User:AndyD147/Intention Tremors Rough Draft

Intention tremor, also known as cerebellar tremor, is a dyskenetic disorder characterized by a broad, course, and low frequency (below 5 Hz) tremor of increasing amplitude as an extremity approaches the endpoint of deliberate, visually guided movement (hence the name intention tremor). Intention tremor is usually perpendicular to the direction of movement and one often overshoot or undershoot their target known as dysmetria. It is the result of dysfunction of the cerebellum in particular on ipsilateral side of the lateral zone. Depending on the location of cerebellar damage, intention tremor can be either unilateral or bilateral.

A variety of causes including: damage or degradation of the cerebellum due to multiple sclerosis, degenerative diseases, trauma, tumor, stroke, or toxicity can cause intention tremors. There is currently no established pharmacological treatment specifically for intention tremors, however, some success has been seen using treatments designed for essential tremor. Intention tremors are often seen in conjunction with other cerebellar dysfunctions such as dysarthria (speech problems), nystagmus (abnormal eye movements) and unsteady gait. Postural tremor may also accompany intention tremor.

History
In 1868, French neurologist Jean-Martin Charcot first characterized the distinction between MS and its resulting intention tremor from resting tremor, found in Parkinson’s disease. Intention tremor became known as part of Charcot's triad along with nystagmus, and scanning speech, other strong indications of MS.

Causes
Intention tremors have a variety of recorded causes. Anything that negatively impacts the cerebellum, brainstem, or thalamus has the potential to induce intention tremors. Some cause include a variety of neurological disorders, such as Multiple Sclerosis, Stroke, Alcoholism, Alcohol withdrawal, Peripheral neuropathy, Wilson's Disease and Fragile X Syndrome, as well as Brain tumors, low blood sugar, normal aging, a variety of drugs, such as sedatives and anticonvulsants, and traumatic brain injury. There has also been a connection of intention tremors to viruses, such as West Nile Virus. A variety of poisons have also been shown to cause intention tremors, including mercury, methyl bromide, phosphine, and lithium. Vitamin deficiencies have also been linked to intention tremors, especially deficiency in Vitamin E. Some normal everyday activities have also been shown to cause intention tremors, including ingesting too much caffeine, cigarettes, stress, anxiety, fear, anger and fatigue.

Mechanism
Intention tremors caused by common causes such as stress, anxiety, fear, anger, caffeine, and fatigue do not seem to result from damage to any part of the brain. These tremors instead seem to be a temporary worsening of a small tremor that is present in every human being. These tremors go away with time.

More permanent intention tremors are caused by damage to certain regions of the brain. The most common cause for intention tremors is damage to the cerebellum. The cerebellum is a part of the brain responsible for motor coordination, posture and balance. It is responsible for fine motor movements. When the cerebellum is damaged, a person has difficulty executing a fine motor movement, such as attempting to touch one's nose with one's finger. One of the most common ways for the cerebellum to become damaged is through the development of cerebellar lesions. The most common site for cerebellar lesions that lead to intention tremors have been reported to be the superior cerebellar peduncle, through which all fibers carrying information to the midbrain pass, and the dentate nucleus, which is also responsible for linking the cerebellum to the rest of the brain. A common example of this is the effect of alcohol abuse on the cerebellum. The alcohol abuse causes degeneration of the anterior vermis of the cerebellum. This leads to an inability to process fine motor movements in the patient and the development of intention tremors. In Multiple Sclerosis, damage occurs due to demyelination and neuron death, which again produces cerebellar lesions and an inability for those neurons to transmit signals. Because of this tight association with damage to the cerebellum, intention tremors are often referred to as cerebellar tremors.

Intention tremors can also be caused as a result of damage to the brainstem or thalamus. Both of these structures are involved in the transmission of information between the cerebellum and the cerebral cortex, as well as between the cerebellum and the spinal cord and then on to the motor neurons. When these become damaged, the relay system between between the cerebellum and the muscle on which it is try to act upon is compromised, thus resulting in the development of a tremor.

Diagnosis
A working diagnosis is made from a neurological examination and evaluation including using physical examination, MRI, patient history and electrophysiological and accelerometric studies. A diagnosis of solely intention tremor can only be made if the tremor is of low frequency (below 5 Hz) and without the presence of resting tremor. Electrophysiological studies can be useful in determining frequency of the tremor and accelerometric studies quantify tremor amplitude. MRI is used to locate damage and degradation to the cerebellum that may be causing the intention tremor. Focal lesions such as neoplasms, tumors, hemorrhages, demyelination, or other damage may be causing dysfunction of the cerebellum and correspondingly the intention tremor.

Physical tests are an easy way to determine the severity of the intention tremor and impairment of physical activity. Common tests that are used to assess intention tremors are the finger-to-nose and heel-to-shin tests. Finger-to-nose test is where the physician will have the patient touch their nose with their finger while monitoring for irregularity in timing and control. A patient with intention tremor will have course, side-to-side movement that increases as the finger approaches the nose. Similarly, the heel-to-shin test evaluates intention tremor of the lower extremities. In such a test, the patient places their heel on the top of their opposite knee and is then instructed to slide their heel down their shin, to their ankle as they are monitored for course and irregular side to side movement as the heel approaches the ankle. Important historical elements to the diagnosis of intention tremor are:
 * 1) age of onset
 * 2) mode of onset (sudden of gradual)
 * 3) anatomical affected sites
 * 4) rate of progression
 * 5) exacerbating and remitting factors
 * 6) alcohol abuse
 * 7) family history of tremor.

Current medications are also an important factor in diagnosis as, many different pharmacological agents can cause tremor.

Treatment and Management
Treatment of intention tremor is very difficult, the tremor might disappear for a while after a treatment has been administered, then return after some time and must be addressed with a different type of treatment. First patients will be asked if they use any of the drugs known to cause tremors, asked to stop taking the medication, and evaluated after some time to determine if the medication was related to the onset of the tremor. A few common drugs that cause intention tremor may be alcohol, anti-arrhythmic drugs, anti-epileptic agents, Benzodiazepine, Cyclosporine, Lithium, neuroleptics, and stimulants. If the tremor persists, treatment that follows may include drug therapy, lifestyle changes, and more invasive forms of treatment such as surgical and other invasive forms of treatment such as thalamic deep brain stimulation.

Intention tremor is notoriously known to be very difficult to treat with Pharmacotherapy and Drugs. Although there is no established pharmacological treatment for intention tremor, a few drugs have been found to have positive effects on intention tremor and seen as treatment by many health professionals. Isoniazid, Buspirone hydrochloride, Glutethimide, Carbamazepine, Clonazepam, Buspirone, Topiramate, Zofran, Propranolol and Primidone have all seen moderate results in treating intention tremor and can be prescribed as treatment. Isoniazid inhibits γ-aminobutyric acid-aminotransferase, which the first step in enzymatic breakdown of GABA, thus increasing GABA, the major inhibitory neurotransmitter in the central nervous system, causing a reduction in cerebellar ataxias. Another neurotransmitter targeted by drugs that have been found to treat intention tremor is Serotonin. The agonist Buspirone hydrochloride, which decreases serotonin's function in the central nervous system has seen as a positive treatment of intention tremor.

Alternative treatments include Cannabis, which has been seen as an effective treatment of tremors in patients with tremors. Physical therapy has found great results in reducing tremors among patients, but usually does not entirely cure the tremors. Relaxation techniques such as meditation, yoga, hypnosis, and biofeedback are other alternative treatments that has seen some results in tremor patients. An at home remedy is wearing wrist weights, which will weigh down one's hands as they make movements, masking much of the tremor. This is not a true treatment, since wearing the weights has not been found to have any lasting effects when they are not on, however they are a quick fix for the tremor, to help the patient cope with the tremor immediately.

A more radical treatment that is used in patients who do not respond to drug therapy, physical therapy, or any other treatments listed above and have moderately to severely debilitating intention tremor might look at surgical intervention as treatment. Deep brain stimulation and surgical lesioning of the thalamic nuclei has been found to be an effective long-term treatment if intention tremor. Deep brain stimulation treats intention tremor, but does not help related diseases or disorders such as dyssynergia and [dysmetria]]. Deep brain stimulation involves the implantation of a device called a brain pacemaker. This medical device with sent electrical impulses to specific parts of the brain changing brain activity in a controlled manner. In the case of intention tremor the thalamic nuclei is the region of the brain targeted for treatment. This form of treatment causes reversible changes and does not cause any permanent lesion, thus is fairly safe, and reduction in tremor amplitude is almost guaranteed and sometimes even resolved with this treatment. Some multiple sclerosis patients have seen sustained benefits in MS progress. Thalamotomy is a surgical treatment of intention tremor, where lesions of the thalamus nucleus are created to disrupt the tremor circuit. Thalamotomy has been used to treat many different forms of intention tremor including tremors that arise from trauma, multiple sclerosis, stroke, and those whose cause it unknown. This is a very invasive, high-risk treatment with many negative effects such as multiple sclerosis worsening, cognitive dysfunction, worsening of dysarthria and dysphagia. Immediate positive effects are seen in patients treated with Thalamotomy, however the intention tremor often comes back after some time, thus no completely treated. Thalamotomy is currently in clinical trials to determine the validity of the treatment in intention tremor with all its high risks.

Related Diseases and Disorders
Intention tremor very common among Multiple sclerosis patients, Ataxia, lack of coordination of muscle movements, which is a major symptom of multiple sclerosis caused cerebellar lesions have been seen intern as underlying causes of intention tremor in multiple sclerosis patients. Multiple sclerosis is a devastating neurological disease caused by demyelination and scarring on the axon of neurons, reducing the ability of the nerve cells of the central nervous system to communicate with each other Almost any neurological symptom can appear from multiple sclerosis, often the disease destroys physical and cognitive function of individuals. Intention tremor can be a first sign of multiple sclerosis in patients, since loss or deteriorated motor function and sensitivity are often the first symptoms of multiple sclerosis.

Parkinson's disease has also been related to intention tremor, however usually Parkinson's disease is classified by a tremor that occurs at rest. Thus intention tremor is not the classical tremor of the disease, however one that patients might exhibit in addition to the resting tremor. Wilson's disease a disease characterized by resting, postural, or kinetic tremor, so once again not directly related to intention tremor, thus a additional tremor of this disease. Other diseases whose patients will exhibit intention tremor are Creutzfeldt-Jacob disease, Paraneoplastic syndrome, Guillain–Barré syndrome, Endocrinology, Hyperthyroidism, Hypoparathyroidism, and Hypoglycemia (insulinoma). Infections such as Rubella, H. Influenza, Rabies, and Varicella have been correlated to intention tremor.

Intention tremor often indicated some fundamental damage to Cerebellum, since the cerebellum is the region of the brain related to fine motor control and voluntary movement. Any sort of cerebral damage can have tragic effects on motor movements because Cerebellum is so integral to fine motor control. Brainstem Tumor, Traumatic brain injury, Vitamin E deficiency, Hypoxia, Cerebellar neoplasm, Hyperthermia or Stroke that occurs in the cerebellum may be underlying conditions to intention tremor. Chronic Alcoholism and overuse of Sedatives or Anticonvulsants have harmful effects on the cerebellum especially degeneration, which can cause permanent damage and are often related to intention tremor.

Intention tremor is frequently accompanied by Dysarthria (a speech disorder characterized by poor articulation and slurred speech), Nystagmus (rapid involuntary eye movement, especially rolling of the eyes), Gait problems (problems and abnormal Walking), and postural tremor or titubation, to-and-fro movements of the neck and trunk. Holmes tremor, a rubral or midbrain tremor is a severe form of intention tremor that affects the proximal muscles of the head, shoulders, and neck. Tremors of this disease occur at frequencies of 2-4 Hz or more.

Current and Future Research
Current research has focused on finding a pharmacological treatment that is specific to intention tremor. Currently, limited success has been seen in treating intention tremor with agents successful in treating essential tremor. Clinical trials of Levetiracetam, typically used to treat epilepsy, and Pramipexole, used to treat resting tremor, have recently been completed to establish their effectiveness in treating kinetic tremor. A clinical trial for Riluzole, initially used to treat amyotrophic lateral sclerosis, is currently underway at the Sapienza University of Rome to evaluate its effectivenes of treating cerebellar ataxia and kinetic tremor.